Modeling Complex Particle Interactions in Dry Powder Inhaler Based Drug Delivery

项目摘要 标题：模拟基于干粉吸入器的药物输送中的复杂颗粒相互作用。 摘要：干粉吸入器(DPI)被用来将药物直接输送到人体呼吸道和 这种药物通常用于治疗哮喘或肺气肿等疾病。主动者 DPI中使用的药物颗粒通常非常小，通常小于5微米。小的 大小使它们非常有凝聚力，这降低了它们的流动性。大的载体颗粒 使用具有较小药物颗粒的聚集体来促进药物输送。 DPI药物传递的核心是团聚和解聚过程 受多种因素的影响，包括范德华相互作用引起的粒子间凝聚力， 吸入器中带电粒子与湍流之间的库仑力和介电泳力 和人类航空公司。流体流动和颗粒运动的精确建模，解决了所有这些问题 对于彻底了解使用DPI的药物输送是至关重要的。库仑力 带电粒子之间的相互作用在粒子技术文献中得到了广泛的研究； 然而，介电泳法已被证明在聚集体中起重要作用。 看似相同的介电粒子，却很少受到关注。作为毒品和携带者 DPI中使用的颗粒通常是介电材料，极有可能起到介电作用 在DPI中的集聚中发挥重要作用。年首次将这一力量纳入DPI分析 文学将是拟议工作的一个新方面。 对粒子之间的静电力进行建模的主要挑战在于确定 粒子电荷，源于粒子与器件之间的接触电荷 内饰。以前的DPI研究只是简单地指定了粒子上的电荷，通常是 不知道。文献中最广泛使用的模拟粒子带电程度的方法 通孔接触充电使用每种材料的有效功函数作为现象学 描述两个接触表面之间电荷转移的参数。这种方法具有 在PIS课题组工作，研究气固两相流态化的相互作用 和粒子荷电；拟议的研究将把这种方法引入DPI研究，以 这在文学史上是第一次。 在这个方案中，我们将开发一个基于开源平台的CFD-DEM模拟工具。 重点是为所有已知的物理学建立模型，包括范德。 瓦耳斯力、流体湍流、库仑和介电泳力以及接触充电。这个 代码将根据文献中的实验数据进行验证，并用于执行 模拟探索了粒子的各种物理特性的重要性。

Project Abstract Title: Modeling complex particle interactions in dry powder inhaler based drug delivery. Abstract: Dry powder inhalers (DPIs) are used to deliver drugs directly to human airways and lungs, and are often used to treat medical conditions such as asthma or emphysema. The active drug particles used in DPIs are often very small, typically less than 5 micrometers. The small size makes them very cohesive, which reduces their flowability. Large carrier particles that aggregate with the smaller drug particles are employed to facilitate drug delivery. The agglomeration and deagglomeration processes that are central to DPI drug delivery are affected by a variety of factors including inter-particle cohesion due to van der Waals interaction, Coulombic and dielectrophoretic forces between charged particles and turbulence in the inhaler and human airways. Accurate modeling of fluid flow and particle motion, accounting for all these forces, is vital for thorough understanding of drug delivery using DPIs. Coulombic forces between charged particles have been widely studied in the particle technology literature; however, dielectrophoresis, which has been shown to play an essential role in clustering of seemingly identical dielectric particles, has received much less attention. As the drug and carrier particles used in DPI are usually dielectric materials, dielectrophoresis is very likely to play a significant role in agglomeration in DPIs. Including this force in DPI analysis for the first time in the literature would be a novel aspect of the proposed work. The main challenge in modeling electrostatic forces between particles lies in determining the particle charge that originates from contact charging between the particles and the device internals. Prior DPI studies have simply specified the charges on the particles, which are usually not known. The most widely used approach in literature to model the extent of particle charging via contact charging employs effective work function of each material as a phenomenological parameter to characterize charge transfer between two contacting surfaces. This approach has been employed in the research group of the PIs to study the interplay of gas-particle fluidization and particle charging; the proposed research would introduce this approach to DPI studies for the first time in the literature. In this proposal, we will develop a CFD-DEM simulation tool based on open-source platforms. Emphasis will be based on implementing models for all the known physics, including van der Waals force, fluid turbulence, Coulombic and dielectrophoretic forces and contact charging. The code will be validated against experimental data from the literature and also used to perform simulations exploring the importance of various physical characteristics of the particles.